P1428: PREDICTORS OF VOC RATE DURING LONG-TERM FOLLOW-UP OF PATIENTS WITH HBSS IN A NEWBORN COHORT STUDY
Authors: Muriel Ramalli, Cynthia Sangarappillai, Banu Kaya, Filipa Barrosso, Sarah Bennett, David Kafuko, Jonathan W Bestwick, Paul Telfer
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Acute pain, (or vaso-occlusive crisis (VOC)) is a dominant clinical feature of Sickle Cell Disease (SCD), resulting in acute and chronic morbidity and increased mortality. Frequent VOC (with hospital attendance) is considered an important marker of disease severity and is a criterion for selection of patients for curative therapies such as stem cell transplantation and gene therapy trials. Reliable prediction of future disease severity is an elusive goal in SCD, but critical for early selection of patients who would most benefit from curative therapy. The East London Newborn Sickle Cohort Study (ELSCS) provides the opportunity to evaluate indicators of VOC severity in the UK Health care setting. Aims: To describe the frequency and variability of VOC occurrence in HbSS over prolonged follow-up and to evaluate potential early predictors of VOC severity Methods: The ELNSCS includes patients born in the London Boroughs of Hackney and Tower Hamlets, diagnosed by universal newborn screening programmes from 1983, and treated in our centre since diagnosis. All clinical data has been entered in a bespoke database and VOC’s validated against clinical record. Follow-up (FU) was from birth until the end of 2018. Subjects were censored on moving to another clinic, BMT, or at death. Potential early predictors assessed at age 2 years included VOC occurrence before age 2, haematological indices and BMI. We tested several multivariate regression models including multiple failure Cox regression (Anderson-Gill), which accounts for the effect of treatments hydroxyurea (HU), simple transfusion (ST), manual (MET) or automated exchange transfusion (AET) as time-dependent covariates. Results: 267 HbSS patients were followed for a total of 3733 patient years. Median age at end of FU was 14.0 (range 3 months to 35 years). 21.3% had been treated with HU, 21.5% with ST, 5.4% with MET and 9.8% with AET. There were a total of 2398 VOCs, with highly variable occurrence over FU. Individual VOC number varied from 0 to 130. 67 patients (25%, median age 4 yrs, range 0.25 -35) did not experience any VOC. Rate increased significantly with age (Increase of 1.08 VOC event per year of age, 95% CI 1.07-1.10, p<0.001). Percentage with annualized VOC rate of >1 sequentially increased within the age ranges 0-5, 6-10, 11-15, 16-20, 21-25 and 26-30 years, while percentage with no VOC’s sequentially decreased (Figure). Use of HU and MET was associated with a significantly higher rate of VOC (For compliant HU hazard ratio (HR): 1.88 (95% CI 1.28-2.76, P<0.001, for non-compliant HU, HR 2.90 (95%CI 1.54-5.45, P<0.001), for MET, HR 2.37 (95% CI 1.65-3.42, P<0.001, while VOC rate with AET or ST were not significantly different from no treatment. Haematological indices and BMI at age 2 and VOC before age 2 were not significantly associated with subsequent VOC rate. Summary/Conclusion: We confirmed a highly variable rate of VOC within patient and between patients with HbSS. VOC rate significantly increased with age, but we were not able to identify any significant predictors of VOC which could be used at an early age to identify at-risk children for intensive therapy. Historical treatment decisions to use hydroxyurea and some modalities of chronic transfusion are proxies for a group of patients with higher rate of VOC. Automated exchange and simple transfusion were more effective than HU or manual exchange transfusion for reducing VOC rate.Keywords: Hemoglobinopathy, Sickle cell disease